Skip to main content
SpringerLink
Log in

Relative oral bioavailability of glycidol from glycidyl fatty acid esters in rats

  • Toxicokinetics and Metabolism
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

In order to quantify the relative bioavailability of glycidol from glycidyl fatty acid esters in vivo, glycidyl palmitoyl ester and glycidol were orally applied to rats in equimolar doses. The time courses of the amounts of glycidol binding to hemoglobin as well as the excretion of 2,3-dihydroxypropyl mercapturic acids were determined. The results indicate that glycidol is released from the glycidyl ester by hydrolysis and rapidly distributed in the organism. In relation to glycidol, there was only a small timely delay in the binding to hemoglobin for the glycidol moiety released from the ester which may be certainly attributed to enzymatic hydrolysis. In both cases, however, an analogous plateau was observed representing similar amounts of hemoglobin binding. With regard to the urinary excretion of mercapturic acids, also similar amounts of dihydroxypropyl mercapturic acids could be detected. In an ADME test using a virtual double tag (3H, 14C) of glycidyl palmitoyl ester, a diverging isotope distribution was detected. The kinetics of the 14C-activity reflected the kinetics of free glycidol released after hydrolysis of the palmitoyl ester. In view of this experimental data obtained in rats, it is at present justified for the purpose of risk assessment to assume complete hydrolysis of the glycidyl ester in the gastrointestinal tract. Therefore, assessment of human exposure to glycidyl fatty acid ester should be regarded as an exposure to the same molar quantity of glycidol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ADME:

Absorption, distribution, metabolism and excretion

AUC:

Area under the curve

BfR:

Federal Institute for Risk Assessment

Bwt:

Body weight

diHOPrVal:

N-(2,3-dihydroxypropyl)valine

DHPMA:

2,3-dihydroxypropyl mercapturic acid or N-acetyl-S(2,3-dihydroxypropyl)cysteine

GC–MS:

Gas chromatography-mass spectrometry

HILIC:

Hydrophilic interaction liquid chromatography

HPLC:

High-performance liquid chromatography

3-MCPD:

3-chloropropane-1,2-diol

MRM:

Multiple reaction monitoring

MSD:

Mass selective detector

NCI:

Negative chemical ionization

NTP:

National toxicology program

SIM:

Single ion monitoring

References

  • Abraham K, Appel KE, Berger-Preiss E, Apel E, Gerling S, Mielke H, Creutzenberg O, Lampen A (2013) Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats. Arch Toxicol 87(4):649–659

    Google Scholar 

  • Bader M, Rosenberger W, Gutzki FM, Tsikas D (2009) Quantification of N-(3-chloro-2-hydroxypropyl)valine in human haemoglobin as a biomarker of epichlorohydrin exposure by gas chromatography-tandem mass spectrometry with stable-isotope dilution. J Chromatogr B Anal Technol Biomed Life Sci 877(13):1402–1410

    Article  CAS  Google Scholar 

  • Bakhiya N, Abraham K, Gurtler R, Appel KE, Lampen A (2011) Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food. Mol Nutr Food Res 55:509–521

    Article  PubMed  CAS  Google Scholar 

  • Belov VN, Müller M, Ignatenko O, Hallier E, de Meijere A (2005) Facile access to isotopically labelled valylleucyl anilides as biomarkers for the quantification of hemoglobin adducts to toxic electrophiles. Eur J Org Chem 23:5094–5099

    Article  Google Scholar 

  • BfR (Bundesinstitut für Risikobewertung) (2009) Initial evaluation of the assessment of levels of glycidol fatty acid esters detected in refined vegetable fats, BfR opinion No. 007/2009, 10 March 2009. http://www.bfr.bund.de/cm/245/initial_evaluation_of_the_assessment_of_levels_of_glycidol_fatty_acid_esters.pdf. Accessed Nov 2012

  • Crews C, Chiodini A, Granvogl M, Hamlet C, Hrncirik K, Kuhlmann J, Lampen A, Scholz G, Weisshaar R, Wenzl T, Jasti PR, Seefelder W (2012) Analytical approaches for MCPD esters and glycidyl esters in food and biological samples: a review and future perspectives. Food Addit Contam Part A. doi:10.1080/19440049.2012.720385

  • DFG (2000) German Research Foundation (DFG) senate commission for the investigation of health hazards of chemical compounds in the work area (MAK commission). Wiley-VCH, Weinheim

    Google Scholar 

  • Eckert E, Drexler H, Göen T (2010) Determination of six hydroxyalkyl mercapturic acids in human urine using hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-ESI-MS/MS). J Chromatogr B Anal Technol Biomed Life Sci 878(27):2506–2514

    Article  CAS  Google Scholar 

  • Eckert E, Schmid K, Schaller B, Hiddemann-Koca K, Drexler H, Goen T (2011) Mercapturic acids as metabolites of alkylating substances in urine samples of German inhabitants. Int J Hyg Environ Health 214:196–204

    Article  PubMed  CAS  Google Scholar 

  • Hamlet CG, Asuncion L, Velišek J, Doleźal M, Zelinková Z, Crews C (2011) Formation and occurrence of esters of 3-chloro-propane-1,2-diol (3-CPD) in foods: what we know and what we assume. Eur J Lipid Sci Technol 113:279–303

    Article  CAS  Google Scholar 

  • Hindsø Landin H, Osterman-Golkar S, Zorcec V, Törnqvist M (1996) Biomonitoring of epichlorohydrin by hemoglobin adducts. Anal Biochem 240(1):1–6

    Article  Google Scholar 

  • Hindsø Landin H, Grummt T, Laurent C, Tates A (1997) Monitoring of occupational exposure to epichlorohydrin by genetic effects and hemoglobin adducts. Mutat Res 381:217–226

  • Hindsø Landin H, Segerbäck D, Damberg C, Osterman-Golkar S (1999) Adducts with haemoglobin and DNA in epichlorohydrin-exposed rats. Chem Biol Interact 117:49–64

    Article  Google Scholar 

  • Hindsø Landin H, Tareke E, Rydberg P, Olsson U, Törnqvist M (2000) Heating of food and haemoglobin adducts from carcinogens: possible precursor role of glycidol. Food Chem Toxicol 38(11):963–969

    Article  PubMed  Google Scholar 

  • Honda H, Fujii K, Yamaguchi T, Ikeda N, Nishiyama N, Kasamatsu T (2012) Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts. Food Chem Toxicol 50:4163–4168

    Article  PubMed  CAS  Google Scholar 

  • IARC (2000) Some industrial chemicals, IARC monograph on the evaluation of carcinogenic risk of chemicals to humans, vol. 77, International Agency for Research on Cancer, Lyon, France pp. 469–486. http://monographs.iarc.fr/ENG/Monographs/vol77/mono77-19.pdf. Accessed Nov 2012

  • Jones AR (1975) The metabolism of 3-chloro,-3-bromo- and 3-iodopropan-1,2-diol in rats and mice. Xenobiotica 5(3):155–165

    Article  PubMed  CAS  Google Scholar 

  • Lynch BS, Bryant DB, Hook GJ, Nestmann ER, Munro LC (1998) Carcinogenicity of monochloro-1,2-propanediol (alpha-chlorohydrin, 3-MCPD). Int J Toxicol 17:47–76

    CAS  Google Scholar 

  • Masukawa Y, Shiro H, Nakamura S, Kondo N, Jin N, Suzuki N, Ooi N, Kudo N (2010) A new analytical method for the quantification of glycidol fatty acid esters in edible oils. J Oleo Sci 59:81–88

    Article  PubMed  CAS  Google Scholar 

  • Mowrer J, Törnqvist M, Jensen S, Ehrenberg L (1986) Modified Edman degradation applied to hemoglobin for monitoring occupational exposure to alkylating agents. Toxicol Environ Chem 11(3):215–231

    Article  CAS  Google Scholar 

  • Müller M, Belov V, de Meijere A, Bünger J, Emmert B, Heutelbeck A, Hallier E (2005) Entwicklung eines neuen Biomonitoringverfahrens zur Bestimmung des Hämoglobinadduktes N-(2,3-Dihydroxypropyl)-Valin nach Epichlorhydrinexposition. Arbeitsmed Sozialmed Umweltmed 40(3):171

    Google Scholar 

  • Nomeir AA, Silveira DM, Ferrala NF, Markham PM, McComish MF, Ghanayem BI, Chadwick M (1995) Comparative disposition of 2,3-epoxy-1-propanol (glycidol) in rats following oral and intravenous administration. J Toxicol Environ Health 44:203–217

    Article  PubMed  CAS  Google Scholar 

  • NTP (1990) National Toxicology Program, Toxicology and carcinogenesis studies of glycidol (CAS No. 556-52-5) in F344/N rats and B6C3F1 mice (gavage studies). Technical Report Series No. 374. NIH Publication No. 90-2829. Research Triangle Park, NC. http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr374.pdf. Accessed Nov 2012

  • Shimizu M, Kudo N, Shiro H, Yasunaga K, Masukawa Y, Katsuragi Y, Yasumasu T (2010) Comparison of indirect and direct quantification of glycidol fatty acid ester in edible oils. J Oleo Sci 59:535–539

    Article  PubMed  CAS  Google Scholar 

  • Van Sittert NJ (1996) N-2-Cyanoethyl-Valin, N-2-Hydroxyethyl-Valin, N-Methyl-Valin (zum Nachweis einer Belastung/Beanspruchung durch Acrylnitril, Ethylenoxid ssowie methylierende Substanzen). In: Hartwig A (ed) Analytische Methoden zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Band 2: Analysen in biologischen Material, 12. Lieferung ed, Wiley-VCH, Weinheim, pp 1–21

  • Wakabayashi K, Kurata Y, Harada T, Tamaki Y, Nishiyama N, Kasamatsu T (2012) Species differences in toxicokinetic parameters of glycidol after a single dose of glycidol or glycidol linoleate in rats and monkeys. J Toxicol Sci 37:691–698

    Article  PubMed  CAS  Google Scholar 

  • Weißhaar R (2011) Fatty acid esters of 3-MCPD: overview of occurrence and exposure estimates. Eur J Lipid Sci Technol 113:304–308

    Article  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV) through the Federal Office for Agriculture and Food (BLE), grant number 514-06.01-2809HS013.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Food Safety, Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8–10, 10589, Berlin, Germany

    Klaus E. Appel, Klaus Abraham, Nadiya Bakhiya & Alfonso Lampen

  2. Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625, Hannover, Germany

    Edith Berger-Preiss, Tanja Hansen, Elisabeth Apel, Sven Schuchardt & Otto Creutzenberg

  3. Institute for Inorganic Chemistry, Leibniz University of Hannover, Callinstr. 9, 30167, Hannover, Germany

    Carla Vogt

Authors
  1. Klaus E. Appel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edith Berger-Preiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tanja Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisabeth Apel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sven Schuchardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carla Vogt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nadiya Bakhiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Otto Creutzenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alfonso Lampen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Klaus Abraham.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 57 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Appel, K.E., Abraham, K., Berger-Preiss, E. et al. Relative oral bioavailability of glycidol from glycidyl fatty acid esters in rats. Arch Toxicol 87, 1649–1659 (2013). https://doi.org/10.1007/s00204-013-1061-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-013-1061-1

Keywords

Search

Navigation